Park Christopher C, Ahn Sangtae, Bloom Joshua S, Lin Andy, Wang Richard T, Wu Tongtong, Sekar Aswin, Khan Arshad H, Farr Christine J, Lusis Aldons J, Leahy Richard M, Lange Kenneth, Smith Desmond J
Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, California 90095, USA.
Nat Genet. 2008 Apr;40(4):421-9. doi: 10.1038/ng.113. Epub 2008 Mar 23.
We mapped regulatory loci for nearly all protein-coding genes in mammals using comparative genomic hybridization and expression array measurements from a panel of mouse-hamster radiation hybrid cell lines. The large number of breaks in the mouse chromosomes and the dense genotyping of the panel allowed extremely sharp mapping of loci. As the regulatory loci result from extra gene dosage, we call them copy number expression quantitative trait loci, or ceQTLs. The -2log10P support interval for the ceQTLs was <150 kb, containing an average of <2-3 genes. We identified 29,769 trans ceQTLs with -log10P > 4, including 13 hotspots each regulating >100 genes in trans. Further, this work identifies 2,761 trans ceQTLs harboring no known genes, and provides evidence for a mode of gene expression autoregulation specific to the X chromosome.
我们利用一组小鼠 - 仓鼠辐射杂交细胞系的比较基因组杂交和表达阵列测量数据，绘制了哺乳动物中几乎所有蛋白质编码基因的调控位点图谱。小鼠染色体中的大量断裂以及该细胞系的密集基因分型使得位点的定位极其精确。由于调控位点是由额外的基因剂量产生的，我们将它们称为拷贝数表达数量性状位点，即ceQTL。ceQTL的 -2log10P支持区间小于150 kb，平均包含少于2 - 3个基因。我们鉴定出29769个 -log10P > 4的反式ceQTL，其中包括13个热点区域，每个热点区域可反式调控超过100个基因。此外，这项研究还鉴定出2761个不含已知基因的反式ceQTL，并为X染色体特有的基因表达自动调节模式提供了证据。
